Skip to Main content Skip to Navigation
Journal articles

Functional Heterogeneity of Mammalian IFITM Proteins against HIV-1

Abstract : Interferon-induced transmembrane proteins (IFITMs) are a family of interferon-inducible proteins that inhibit a broad range of viruses by interfering with viral-to-cellular membrane fusion. The antiviral activity of IFITMs is highly regulated by several posttranslational modifications and by a number of protein domains that modulate steady-state protein levels, trafficking, and antiviral effectiveness. Taking advantage of the natural diversity existing among IFITMs of different animal species, we have compared 21 IFITMs for their ability to inhibit HIV-1 at two steps, during virus entry into cells (target cell protection) and during the production of novel virion particles (negative imprinting of virion particles’ infectivity). We found a high functional heterogeneity among IFITM homologs with respect to both antiviral modalities, with IFITM members that exhibit enhanced viral inhibition, while others have no ability to block HIV-1. These differences could not be ascribed to known regulatory domains and could only be partially explained through differential protein stability, implying the existence of additional mechanisms. Through the use of chimeras between active and inactive IFITMs, we demonstrate that the cross talk between distinct domains of IFITMs is an important contributor of their antiviral potency. Finally, we identified murine IFITMs as natural variants competent for target cell protection, but not for negative imprinting of virion particles’ infectivity, suggesting that the two properties may, at least in principle, be uncoupled. Overall, our results shed new light on the complex relationship between IFITMs and viral infection and point to the cross talk between IFITM domains as a novel layer of regulation of their activity
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03370239
Contributor : Andrea Cimarelli Connect in order to contact the contributor
Submitted on : Wednesday, October 13, 2021 - 3:35:45 PM
Last modification on : Tuesday, October 19, 2021 - 4:00:45 PM

File

MArziali JVI paper.pdf
Files produced by the author(s)

Identifiers

Collections

Citation

Federico Marziali, Mathilde Delpeuch, Anuj Kumar, Romain Appourchaux, Jérémy Dufloo, et al.. Functional Heterogeneity of Mammalian IFITM Proteins against HIV-1. Journal of Virology, American Society for Microbiology, 2021, 95 (18), ⟨10.1128/JVI.00439-21⟩. ⟨hal-03370239⟩

Share

Metrics

Record views

26

Files downloads

33